{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T14:12:59Z","timestamp":1788876779906,"version":"build-2803163510"},"reference-count":42,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pain Practice"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Several studies point towards the involvement of the immune system (especially the monocyte\u2013macrophage system) in the pathophysiology of Complex Regional Pain Syndrome (CRPS), as shown by increased levels of the cytokines tumor necrosis factor (TNF)\u2010\u03b1 and interleukin (IL)\u20106. These cytokines are primarily released from pro\u2010inflammatory M1 macrophages, but are difficult to measure in a clinical setting. Investigating the activity of tissue\u2010resident macrophages by measuring soluble CD163 (sCD163) in serum is much more clinically applicable. sCD163 could potentially be a biomarker for determining inflammation in CRPS and would have direct consequences for the choice of therapy. The aim of this study is to investigate the tissue\u2010resident macrophage activation in CRPS with sCD163 and explore the relationship between soluble IL\u20102R, which is a marker for T\u2010cell activation, and sCD163.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The sCD163 levels were determined in this retrospective cohort study (MEC\u20102020\u20100716) in serum of CRPS patients (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200922) and healthy controls (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200927). ELISA kits were used to measure the levels of these markers. Data on demographics, pain scores (11\u2010point Numeric Rating Scale: NRS), sIL\u20102R levels, signs and symptoms, and CRPS disease severity were also recorded.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The median serum sCD163 level was significantly higher in CRPS patients (CRPS 960.5\u2009pg\/mL [Q3\u2013Q1: 1211.5\u2013623.9] than in healthy controls 677.0\u2009pg\/mL [Q3\u2013Q1: 828.0\u2013469.5],\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.008). There was a statistically significant positive correlation between sCD163 and sIL\u20102R in the CRPS group (\n                      <jats:italic>r<\/jats:italic>\n                      <jats:sub>\n                        <jats:italic>s<\/jats:italic>\n                      <\/jats:sub>\n                      \u2009=\u20090.577;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.005), but not in the healthy control group (\n                      <jats:italic>r<\/jats:italic>\n                      <jats:sub>\n                        <jats:italic>s<\/jats:italic>\n                      <\/jats:sub>\n                      \u2009=\u20090.359;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.066).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings indicate that pro\u2010inflammatory activation of tissue\u2010resident macrophages and thus the monocyte\u2013macrophage system is part of CRPS pathogenesis. The monocyte\u2013macrophage system is an interesting new target for future research into the pathogenesis of CRPS, but also has potential for diagnosis, particularly for assessing the involvement of the immune system and choice of therapy in the individual CRPS patient. Measurement of the sCD163 could be a potential biomarker for inflammation in CRPS.<\/jats:p>\n                    <jats:p>\n                      <jats:bold>Trial Registration:<\/jats:bold>\n                      This retrospective cohort study was approved by the Medical Ethics Committee of the Erasmus MC University Medical Center (MEC\u20102020\u20100716).\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/papr.70189","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T11:50:49Z","timestamp":1784289049000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Elevated Serum Soluble\n                    <scp>CD163<\/scp>\n                    Indicates Macrophage Activation: A Potential Biomarker for Inflammation in Complex Regional Pain Syndrome?"],"prefix":"10.1111","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0276-1511","authenticated-orcid":false,"given":"Nadia","family":"Kriek","sequence":"first","affiliation":[{"name":"Center for Pain Medicine, Department of Anesthesiology Erasmus MC University Medical Center  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4899-0624","authenticated-orcid":false,"given":"Krishna","family":"Bharwani","sequence":"additional","affiliation":[{"name":"Center for Pain Medicine, Department of Anesthesiology Erasmus MC University Medical Center  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4306-654X","authenticated-orcid":false,"given":"Maaike","family":"Dirckx","sequence":"additional","affiliation":[{"name":"Center for Pain Medicine, Department of Anesthesiology Erasmus MC University Medical Center  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Stronks","sequence":"additional","affiliation":[{"name":"Center for Pain Medicine, Department of Anesthesiology Erasmus MC University Medical Center  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Nagtzaam","sequence":"additional","affiliation":[{"name":"Laboratory Medical Immunology, Department of Immunology Erasmus MC University Medical Center  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5235-3156","authenticated-orcid":false,"given":"Wim A.","family":"Dik","sequence":"additional","affiliation":[{"name":"Laboratory Medical Immunology, Department of Immunology Erasmus MC University Medical Center  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2852-4880","authenticated-orcid":false,"given":"Frank","family":"Huygen","sequence":"additional","affiliation":[{"name":"Center for Pain Medicine, Department of Anesthesiology Erasmus MC University Medical Center  Rotterdam the 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